Throughout this application, various publications are referenced by arabic numerals within parentheses. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein.
There is accumulating evidence that melanoma is an immunogenic cancer in humans. In addition to indirect indications such as spontaneous regressions, lymphoid infiltrates, and increased incidence of melanoma in immunosuppressed patients, several groups have reported specific humoral and cellular immune reactions to melanoma cell-surface antigens (1-6). Based on the assumption that an immune restraint to melanoma growth exists and can be strengthened, vaccines containing melanoma-derived antigens are being tested in patients with the disease at several centers (7-9).
Serological methods have been pursued most extensively to define melanoma antigens that are immunogenic in melanoma patients. We have studied the reactivity with surface antigens of cultured melanoma cells from the same patient (termed autologous typing) in more than 200 patients. Three classes of antigens have been defined in this way (2). Class 1 (unique) melanoma antigens are restricted to the autologous melanoma; six examples of class 1 antigens have been detected (10-15). Class 2 melanoma antigens are detected on the autologous melanoma, on a subset of allogeneic melanoma cells, and on other neuroectodermally derived tumors; these class 2 antigens have characteristics of autoimmunogenic differentiation antigens, and one of the best-analyzed class 2 melanoma antigens is the ganaglioside GD2 (16). Class 3 melanoma antigens are not restricted to any differentiation lineage and are more widely distributed.
The advent of methods for producing human monoclonal antibodies (mAbs) through immortalizing human lymphocytes with Epstein-Barr virus (EBV) (17) or by fusion with human or mouse lymphoblastoid/myeloma partners (18) provides a new level of precision in the analysis of the immune response to melanoma.
Additionally, antibodies for melanoma patients reacting with melanoma cell surfaces or intracellular antigens have been isolated (19-24).